US6846311B2 - Method and apparatus for in VIVO treatment of mammary ducts by light induced fluorescence - Google Patents
Method and apparatus for in VIVO treatment of mammary ducts by light induced fluorescence Download PDFInfo
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- US6846311B2 US6846311B2 US10/212,280 US21228002A US6846311B2 US 6846311 B2 US6846311 B2 US 6846311B2 US 21228002 A US21228002 A US 21228002A US 6846311 B2 US6846311 B2 US 6846311B2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0613—Apparatus adapted for a specific treatment
- A61N5/062—Photodynamic therapy, i.e. excitation of an agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
- A61B1/04—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances
- A61B1/043—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances for fluorescence imaging
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
- A61B1/06—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor with illuminating arrangements
- A61B1/0638—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor with illuminating arrangements providing two or more wavelengths
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/41—Detecting, measuring or recording for evaluating the immune or lymphatic systems
- A61B5/414—Evaluating particular organs or parts of the immune or lymphatic systems
- A61B5/417—Evaluating particular organs or parts of the immune or lymphatic systems the bone marrow
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
- A61B90/39—Markers, e.g. radio-opaque or breast lesions markers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0601—Apparatus for use inside the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B2018/00982—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body combined with or comprising means for visual or photographic inspections inside the body, e.g. endoscopes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2218/00—Details of surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B2218/001—Details of surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body having means for irrigation and/or aspiration of substances to and/or from the surgical site
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
- A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters
Definitions
- the present invention is generally directed toward the treatment of breast cancer and more specifically toward the treatment of atypical tissue and cells in the mammary breast ducts of women by detecting atypical tissue by administering a compound which is converted into a photosensitizer by the diseased or atypical cells in the mammary duct transmitting a light of predetermined wave length to be absorbed by the sensitizer which can be directly viewed to locate the diseased atypical cells, and further treated with additional light to kill the atypical cells.
- breast cancer A leading disease incurred by women is breast cancer.
- Breast cancer is the second leading cause of death for women of all ages and the leading cause of death for women aged 25-55. Approximately one in eight women will incur breast cancer in their lifetimes. Approximately 220,000 surgeries are performed annually in the United States with almost 20 percent requiring the complete removal of the breast.
- mammography The current medical standard for determining breast cancer in women is mammography.
- mammography For breast cancer detection, other than clinical examination and self-examination, women rely almost exclusively on mammography. It is estimated that more than 30 million mammograms are performed each year in the U.S. alone. Mammography is so insensitive that typically the average size of the tumor which can be detected is approximately 1.5 cm At that size, a tumor has probably been growing, undetected, for nearly 8 years on average. In fact, two-thirds of mammographically detected breast cancer is invasive. In addition, mammography is notorious for “false positive” readings, which lead to many unneeded biopsies. However mammography fails to detect up to 20% of breast cancers in women over 50 and up to 40% of breast cancers in younger women.
- breast cancer is generally treatable in three ways: surgery, radiation and chemotherapy.
- Surgery and radiation have risks and disadvantages well known to those skilled in the art.
- Chemotherapy may be disadvantageous as when the drugs involved cause sickness to the patient when they enter the blood stream.
- Mammary Intraductal Treatment refers to a procedure in which abnormal cells in the lining of the mammary duct are destroyed to control abnormal intraductal pathology that may or may not be related to malignancy.
- MIT Mammary Intraductal Treatment
- women with positive mammograms, positive biopsies or intraductal atypical (abnormal pathology) often have a choice of watchful waiting, medical therapy, or surgery (lumpectomy and mastectomy).
- the advancement of new technology and techniques for the treatment of breast disease has not kept pace with other medical areas, particularly in the area of minimally invasive techniques (mammary ductoscopy).
- Benign conditions that can lead to abnormal intraductal assessment include intraductal papilloma, hyperplasia and atypical ductal hyperplasia and these can be removed without requiring invasive surgery.
- hormonal therapies, and pharmaceutical agents may control the growth of intraductal cancerous lesions.
- Intraductal treatment can be indicated for women who have not responded to medical therapy or choose not to take the agents due to side effects or other personal reasons. All women should have biopsies or intraductal samplings (lavage) to confirm the presence of atypical or malignant disease.
- the present detection technique utilizes the mammary ductoscope allowing the physician to look directly into the mammary ducts to determine tissue fluorescense.
- Fluorescent substances in an organism are exemplified by NADH (nicotinamide adenine nucleotide), FMN (flavin mononucleotide) and pyridine nucleotide.
- NADH nicotinamide adenine nucleotide
- FMN flavin mononucleotide
- pyridine nucleotide pyridine nucleotide.
- the relationship between the intrinsic substances in an organism and the diseases has been clarified. If textures of an organism are irradiated with excitation light, fluorescent light having a wavelength longer than that of the excitation light is generated.
- HpD Hematoporphyrin
- Photofrin and ALA beta-aminolevulminic acid
- U.S. Pat. No. 4,556,057 discloses a system comprising a diagnosing laser beam source, a curing laser beam source and a normal photographing light source.
- the normal photographing light source is controlled in synchronization with the activation/deactivation of the diagnosing light source and fluorescent light generated due to irradiation with excitation light is captured by an image sensing apparatus having an image intensifier by a normal image sensing apparatus.
- the observed fluorescent image and observed normal image are displayed on monitors which correspond to the image sensing apparatuses so that a cancer can be diagnosed and cured.
- the destruction of the intraductal epithelial tissue can be performed by various energy delivering devices, namely, fluorescence.
- Photodynamic therapy uses such photosensitizing compounds and lasers to produce tumor necrosis.
- Treatment of solid tumors by PDT usually involves the systemic administration of tumor localizing photosensitizing compounds and their subsequent activation by laser.
- the sensitizer Upon absorbing light of the appropriate wavelength the sensitizer is converted from a stable atomic structure to an excited state. Cytotoxicity and eventual tumor destruction are mediated by the interaction between the sensitizer and molecular oxygen within the treated tissue to generate cytotoxic singlet oxygen.
- the Pandey et al. patents are directed to pyropheophorbide compounds for use in standard photodynamic therapy.
- the Allison et al. patent is similar to the Levy patents in that green porphyrins are conjugated to lipocomplexes to increase the specificity of the porphyrio compounds for the targeted tumor cells.
- the Kopeck et al. patent also discloses compositions for treating cancerous tissues. These compositions consist of two drugs, an anti-cancer drug and a photoactivatable drug, attached to a copolymeric carrier. The compositions enter targeted cells by pinocytosis. The anti-cancer drug acts after the targeted cell has been invaded. After a period of time, a light source is used to activate the photosensitized substituent.
- Photofrin based PDT was employed; photofrin having been administered intravenously 24 hours before the light treatment.
- the SPG immunotherapy was shown to enhance the direct killing effect of the PDT.
- the indirect killing effect (seen as a decrease in survival of tumor cells left in situ) was, however, much more pronounced in tumors of animal not receiving SPG.
- the difference in the effectiveness of SPG immunotherapy when performed before and after PDT suggested that maximal interaction is achieved when immune activation peaks at the time of the light delivery or immediately thereafter. With SPG starting after PDT (and attaining an optimal immune activation 5-7 days later), it is evidently too late for a beneficial reaction.
- Photodynamic therapy uses specifically designed drugs such as Foscan.RTM. (Scotia Pharmaceuticals), ALA (DUSA)and Photofiin (QLT Phototherapeutics) to destroy rapidly dividing cells. These drugs are selectively retained or generated at rapidly dividing cells and are subsequently excited by light to produce the desired effects.
- the primary mode of activity usually involves energy transfer from these photoexcited drugs to O 2 to produce superoxides or O 2 in its singlet state. To date this excitation has been provided by lasers, lamps, and new materials such as laser action in amplifying scattering media. Some of these sources are generally expensive and require complicated delivery systems.
- Photofrin Two of the most important photodynamic therapy drugs are the naturally occurring ALA compound and Photofrin. Both of these are porphyrin compounds that have a peak absorption at 630 nm with a line width of approximately 35 nm. Photofrin has recently received FDA approval for the treatment of esophageal cancer.
- U.S. Pat. No. 5,087,636 to Jamieson, et al. discloses a method to identify and destroy malignant cells in mononuclear cell populations. This method includes the steps of contacting a composition of bone marrow cells or other cells with a green porphyrio of a specific compound, irradiating the cell composition with light at a wave length effective to excite fluorescence of the green porphyrio, and then detecting the presence or absence of fluorescence indicating malignancy.
- This reference also discloses the steps by which the bone marrow cells are removed, separated, washed and diluted to an appropriate concentration for treatment, incubated, centrifuged, and exposed to the irradiating light.
- U.S. Pat. Nos. 5,308,608 and 5,149,708 to Dolphin, et al. disclose specific types of porphyrin compounds which may be used for detection, photosensitization, or the destruction of a targeted biological material when the targeted tissue is contacted with the specified porphyrin, and irradiated with light that excites the compound.
- U.S. Pat. No. 5,211,938 to Kennedy, et al. discloses a method of detection of malignant and non-malignant lesions by photochemotherapy of protoporphyrin IX precursors.
- 5-aminolevulinic acid (5-ALA) is administered to the patient in an amount sufficient to induce synthesis of protoporphyrin IX in the lesions, followed by exposure of the treated lesion to a photo activating light in the range of 350-640 nanometers.
- Naturally occurring protoporphyrin IX is activatable by light which is in the incident red light range (600-700 nanometers) which more easily passes through human tissue as compared to light of other wave lengths which must be used with other types of porphyrins.
- 5-ALA makes cell fluorescence easier to observe, and also greatly reduces the danger of accidental phototoxic skin reactions in the days following treatment since protoporphyrin IX precursors have a much shorter half life in normal tissues than other popularly used porphyrins.
- Another set of prior art references exists which relate to flow cytometry utilizing fluorescence producing compounds.
- One such prior art reference includes U.S. Pat. No. 5,605,805 to Verwer, et al., which discloses a method for determining the lineage of acute leukemia cells in the sample by fluorocytometry.
- Other examples of fluorocytometry utilizing fluorescence include U.S. Pat. No. 5,418,169 to Crissman, et al., U.S. Pat. No. 5,556,764 to Sizto, et al., and U.S. Pat. No. 5,627,040 to Bierre.
- the tumor still needs to be sampled by an appropriate biopsy method.
- biopsy methods also require some type of sedation or anesthesia.
- traditional methods of confirming a malignancy may require at least two interventional surgical procedures.
- the present invention is directed toward the detection and treatment of abnormal growths and cancer located in the mammary ducts of women's breasts which in the present invention is when the cancer is typically between two and three years old with a size of about 0.2 mm. This is over 50 times more sensitive than a standard mammogram.
- the present invention uses a micro-endoscope having a diameter ranging from 0.5 mm to 1.2 mm to illuminate the targeted part of the body in which cancer is suspected.
- the light is delivered at a specified wave length to illuminate and treat an area which has previously been subjected to a fluorescent marker or combination of markers which causes atypical or malignant cells to illuminate or fluoresce under observation of light at a specified wavelength.
- introduction of an endoscope into the body requires some type of sedation or general or local anesthesia. However, prior to actual treatment, there must be a confirmed test of cancer.
- the present invention provides a fluorescent micro-endoscope apparatus for obtaining a fluorescent image to perform observation and diagnosis and a laser or light source capable of transmitting light in a predetermined wavelength on a diseased portion of a mammary duct.
- An object of the present invention is to provide a fluorescent micro-endoscope apparatus which is capable of capturing both normal light image and a fluorescent light image and which has a simple structure.
- Another object of the present invention is to provide a fluorescent micro-endoscope assembly which is capable of performing an errorless and accurate diagnosis by correcting the distribution of fluorescent light intensities.
- FIG. 1 is an exploded side elevational view of the endoscope used in the present invention
- FIG. 2 is an enlarged partial cross section of the lens end of the endoscope in FIG. 1 ;
- FIG. 3 is a perspective orientated view of the back end of the endoscope showing a light post and laser post;
- FIG. 4 is a perspective view of a portion of the front end of the micro-endoscope assembly
- FIG. 5 is an enlarged cross sectional view taken across FIG. 4 ;
- FIG. 6 is an alternate embodiment of the micro-endoscope assembly invention.
- the present invention is directed towards a micro-endoscope assembly 10 which can be used and inserted into the lactiferous ducts of the breast of a woman patient and a method for locating and treating cancer cells in the duct.
- the lactiferous ducts generally range in number from about six to about twelve in women and lead from areas of the breast to the nipple where they are in parallel vertical orientation with each other.
- the ducts have a very thin cell wall ranging from 3 to 4 cells in thickness and are resilient.
- the ducts have a smooth inner surface and white color which resemble visually the interior of a standard PVC pipe.
- the micro-endoscope assembly 10 consists of tube or guide cannula 14 which seats and guides the endoscope 12 .
- the cannula 14 has an outer cylindrical wall 16 which defines an internal passageway which runs along its length to seat and guides the endoscope 12 .
- Cannula tube 14 may be a rigid steel tube ranging from 5-20 cm long having an outer diameter ranging from 0.5 mm to approximately 1.2 mm or alternatively may be a semi-rigid tube made of flexible or transparent plastic, or some other suitable material, and having the same or a longer length.
- the exterior of the cannula is marked with marking indicia 15 as seen in FIG.
- the marking indicia can be in the form of rings of opaque, translucent or light reacting material or any other suitable geometry which is easily visible to the surgeons eye.
- the marking indicia can be printed onto the outer surface of the cannula or imbedded in the cannula structure material.
- Various cannula are envisioned to be interchangeable with the endoscope 12 by unscrewing one guide cannula from the endoscope front hub 18 and its associated connector member 20 and screwing one another on to the connector member.
- the endoscope 12 is provided with tube body 17 formed with objective lens 22 at its distal end and image guide 24 as is more clearly shown in FIG. 2 .
- the endoscope 12 has a proximal end in the form of a back member 26 having a light post 27 and a video port 29 as seen in FIG. 3 .
- the preferred cannula embodiment 30 as seen in FIG. 5 has a cylindrical outer cannula or sheath 32 formed with a beveled distal end 34 as shown in FIG. 4 or a cylindrical end as shown in FIG. 2 .
- the inner wall of sheath 32 defines a cylindrical inner channel 33 which has an inner cylindrical tube 36 eccentrically mounted thereon.
- the tube 36 defines the endoscope channel 37 and holds endoscope 12 .
- the inner cylindrical tube 36 is eccentrically mounted in cylindrical inner channel 33 to the wall of the cannula sheath 32 and its outer surface together with the inner surface of the sheath or tube 32 to define a moon shaped channel 38 which acts as a channel or passageway providing irrigation and aspiration and is also used as a port through which a fiber optic array or a laser probe 60 can be inserted until for transmission of light energy of predetermined wave length on the patient's duct area containing cells and/or tissue showing abnormal characteristics.
- Suitable working devices in the form of laser or light probe 60 can be inserted in the working channel 38 of the micro-endoscope for light wave guides.
- the generator or energy source is indicated by block diagram 64 and can be used to deliver varied light wave lengths for excitation depending on the fluorescent compound used.
- a laser fiber or fiber bundle 100 as seen in FIG. 5 and in FIG. 6 can be used to excite the chemically treated tissue within the mammary duct.
- a photosensitive compound is introduced to the cell tissue through the working channel 38 .
- These compounds when administered in appropriate amounts selectively enter into pre-malignant and malignant cells, and provide a “fluorescent marker” in the cells, primarily in the mitochrondia surrounding the nucleus.
- the compounds which may be used in this method to induce fluorescence include ALA and it's derivatives, 5-ALA, protoporphyrin IX, tetrakis carboxy-phenyl porphine (TCPP), hematoporphyrine derivative, photofrin, and photofrin II and other compounds known in the art to cause fluorescence in pre-malignant or malignant cells.
- TCPP For TCPP, this compound enters live cells via a special transport mechanism found in the outer cellular wall. TCPP will not enter dead cells, thus making it a good compound for in viro application.
- the above compounds will cause pre-malignant or malignant cells to fluoresce when exposed to frequencies of light which match the excitation frequency of the particular compound used; however healthy cells will generally not fluoresce.
- TMPP tetraporphen (4, N-methyulpyridil)
- the compound After introduction of predetermined dosage of the chemical compound(s) to the mammary ducts, the compound incubates for a period of time ranging between 1 and 4 hours to allow the pre-malignant and malignant cells to interact with the compounds.
- the average time for interaction time for TCPP is 1-2 hours. Other compounds may take longer and the absorption time is set out in the prior art.
- the micro-endoscope is inserted into the mammary duct and the light source 64 is tuned to provide light which matches the excitation frequency and the treatment frequency.
- One such light source for photofrin and similar photodynamic therapy drugs is a pulsed (150 nanosecond pulse width) Nd:YAG laser that outputs to a frequency doubler such as a KTP crystal which is used to drive a dye laser in a number of wave lengths.
- the excitation frequency ranges from 380-400 nm and for endogenous protoporphyrin IX the absorbtion ranges is 412 nm.
- the wave length ranges from 300 nm to 450 nm.
- antiseptic or a flushing solution such as saline can be applied to the duct interior and the contents withdrawn via the micro-endoscope. After treatment, the micro-endoscope is withdrawn from the mammary duct. Alternatively, the flushing step can be performed after withdrawal of the micro-endoscope from the mammary duct.
- FIG. 6 An alternate embodiment of the cannula 40 is shown in cross section in FIG. 6 .
- This embodiment has a cylindrical outer cannula or sheath 42 which defines a cylindrical inner channel 43 in which an inner cylindrical tube 46 is eccentrically mounted to the wall of sheath 42 .
- the cylindrical tube 46 defines the endoscope channel conduit 47 to hold the endoscope 12 .
- a second smaller cylindrical tube 48 is eccentrically mounted in channel 43 adjacent to and integral with a portion of the wall of tube 46 and a wall of the cannula 42 to form a laser or light probe channel 49 which holds the laser or light probe 60 .
- the cylindrical tube structure 46 divides the moon shaped channel up into two separated segments 52 and 54 which can also serve as the irrigation and aspiration channels for the assembly.
- FIG. 1 also shows the endoscope 12 with the lens tube 17 and tube portion 19 coupled between hub 18 and back end 26 .
- Tube 19 includes a passageway in it's interior capable of holding fiber optic strands and/or illumination strands. Such strands run from video port 29 , through tube portion 19 into hub 18 . The strands run through hub 18 into the inner passageway of tube portion 17 though or outside of the working channel, as described in more detail below. These strands provide both a light source of desired wavelength or multiple wavelengths to the area of interest and a video source to the video port, allowing the physician to see a fluoresced image of the area of the duct in which treatment is being undertaken.
- the back end 26 is formed with a light source post connector 27 .
- the tube portion 14 which has an outer diameter of approximately 1.2 mm has a working channel, a plurality of light fibers and a lens 22 .
- the light fibers 22 run the length of the guide tube 17 and provide light to the areas of interest.
- the light fibers are commercially available.
- the tube cannula 14 can alternately carry the light fibers or have them molded in the tube material.
- the lens 22 also runs longitudinally down inner passage of guide tube 17 .
- the endoscope 12 is used in conjunction with a video monitor and prismatic screen (not shown).
- the video port 29 is coupled to a video camera which is in turn coupled to a video monitor as is well known in the art and has an attached prismatic screen manufactured by Acueity Inc.
- the video camera may be of many different commercially available models, although CCD cameras are particularly useful in this type of application. Specifically, a Panasonic GS99-NTSC medical video endoscopycamera, from Matsushita Electric Corporation of America, has been found to be useful. Moreover, it has been found that in such a camera 1 ⁇ 4 inch CCD chip is more advantageous than a 1 ⁇ 2 inch CCD chip, because it provides an image with smaller pixels. Such chips are included in CCD cameras and also are commercially available from many sources such as, for example, the Sony Corporation of America.
- the video monitor may be any of a number of commercially available video monitors.
Abstract
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US10/212,280 US6846311B2 (en) | 2002-04-02 | 2002-08-06 | Method and apparatus for in VIVO treatment of mammary ducts by light induced fluorescence |
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US10/112,954 US6878149B2 (en) | 2002-03-25 | 2002-04-02 | Apparatus and method for intraductal abalation |
US10/212,280 US6846311B2 (en) | 2002-04-02 | 2002-08-06 | Method and apparatus for in VIVO treatment of mammary ducts by light induced fluorescence |
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US10/112,954 Continuation-In-Part US6878149B2 (en) | 2002-03-25 | 2002-04-02 | Apparatus and method for intraductal abalation |
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US20100094168A1 (en) * | 2007-03-23 | 2010-04-15 | Siegfried Riek | Instrument for the medical examination of tight body ducts |
US20100204609A1 (en) * | 2009-02-10 | 2010-08-12 | Howard Worth | Microendoscope and methods of use |
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